Methods and systems for changing a refractive property of an implantable intraocular lens

ABSTRACT

A method of altering a refractive property of a crosslinked acrylic polymer material by irradiating the material with a high energy pulsed laser beam to change its refractive index. The method is used to alter the refractive property, and hence the optical power, of an implantable intraocular lens after implantation in the patient&#39;s eye. In some examples, the wavelength of the laser beam is in the far red and near IR range and the light is absorbed by the crosslinked acrylic polymer via two-photon absorption at high laser pulse energy. The method also includes designing laser beam scan patterns that compensate for effects of multiphone absorption such as a shift in the depth of the laser pulse absorption location, and compensate for effects caused by high laser pulse energy such as thermal lensing. The method can be used to form a Fresnel lens in the optical zone.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. § 119(e) of U.S.Provisional Patent Application Nos. 62/654,192, filed Apr. 6, 2018 and62/720,882, filed Aug. 21, 2018, which are incorporated herein byreference in their entirety.

BACKGROUND OF THE INVENTION

Cataract extraction is one of the most commonly performed surgicalprocedures in the world. A cataract is the opacification of thecrystalline lens or its envelope—the lens capsule—of the eye. It variesin degree from slight to complete opacity that obstructs the passage oflight. Early in the development of age-related cataract the power of thelens may be increased, causing near-sightedness (myopia), and thegradual yellowing and opacification of the lens may reduce theperception of blue colors as those wavelengths are absorbed andscattered within the crystalline lens. Cataract typically progressesslowly to cause vision loss and are potentially blinding if untreated.

Treatment is performed by removing the opaque crystalline lens andreplacing it with an artificial intraocular lens (IOL). An estimated 3million cases are presently performed annually in the United States and15 million worldwide. This market is composed of various segmentsincluding intraocular lenses for implantation, viscoelastic polymers tofacilitate surgical maneuvers, disposable instrumentation includingultrasonic phacoemulsification tips, tubing, and various knives andforceps.

However, post-surgical visual acuity in patients with a newly implantedIOL is often imperfect. There is a need for improved methods ofcorrecting the refractive properties of an IOL after implantation inorder to improve post-surgical outcomes.

SUMMARY OF THE INVENTION

In many embodiments, a method of altering a refractive property of acrosslinked acrylic polymer comprises generating a light beam with alight source; and irradiating the crosslinked acrylic polymer with thelight beam, thereby producing a predetermined change in a refractiveproperty of the crosslinked acrylic polymer. Preferably, irradiationwith the laser light beam results in a change in refractive index of thecross-linked acrylic polymer, thereby causing the predetermined changein the refractive property. In many embodiments, a first change in therefractive index is negative during a first time period afterirradiation and a second change in the refractive index is positive in asecond time period after irradiation. In many embodiments, a change inrefractive index of the cross-linked acrylic polymer relative to thepre-irradiation refractive index at a location within the crosslinkedacrylic polymer is linearly related with a total energy of theirradiation with the light source.

In preferred embodiments, the light source is a pulsed laser source, andthe pulsed laser source produces femtosecond or longer up to a fewnanosecond laser pulse. In preferred embodiments, the pulsed laserpulses irradiate the crosslinked acrylic polymer and produce a firstchange in the refractive index which is negative during a first timeperiod after irradiation and a second change in the refractive indexwhich is positive in a second time period after irradiation. The firsttime period may occur either before or second time period, i.e. thechange may be negative and then becomes positive, or vice versa. Thispredetermined change in refractive index relative to the pre-irradiationrefractive index at a location within the crosslinked acrylic polymer isdetermined by controlling a total energy of the irradiation with thelight source.

A method of altering a refractive property of an implantable intraocularlens having an optic body including an optical zone and a peripheralzone entirely surrounding the optical zone, comprises generating a lightbeam with a light source; and irradiating the optical zone with thelight beam. The optical zone comprises a crosslinked acrylic materialand irradiation with the light beam produces a predetermined change in arefractive property of the crosslinked acrylic polymer, thereby alteringa refractive property of the intraocular lens. Preferably, irradiationwith the laser light beam results in a change in refractive index of thecross-linked acrylic polymer, thereby causing the predetermined changein the refractive property. Preferably, first change in the refractiveindex is negative during a first time period after irradiation and asecond change in the refractive index is positive in a second timeperiod after irradiation, and becomes stable over a long period of time.Preferably, the change in refractive index relative to thepre-irradiation refractive index at a location within the crosslinkedacrylic polymer is linearly related with a total energy of theirradiation with the light source.

In another aspect, the present invention provides a method of altering arefractive property of an implantable intraocular lens having an opticbody including an optical zone and a peripheral zone surrounding theoptical zone, the method including: generating a light beam using alight source and a light delivery optical system; and irradiating theoptical zone with the light beam, wherein the optical zone comprises amaterial configured to change its refractive index upon irradiation bythe light beam, thereby altering a refractive property of theintraocular lens.

In some embodiments, the optical zone comprises a crosslinked acrylicmaterial, and wherein irradiation with the light beam produces apredetermined change in the refractive index of the crosslinked acrylicpolymer. In some embodiments, the intraocular lens is implanted in apatient's eye before the irradiating step, and the light beam with awavelength of 400 to 450 nm or 650 to 800 nm is used.

In some embodiments, the light source is a pulsed laser source, andirradiating step includes scanning a focus spot of the pulsed laser beamwithin the optical zone of the intraocular lens according to a scanpattern. In some embodiment, the scan pattern is designed to compensatefor a multi-photon absorption-induced shift in absorption depth. In someembodiments, the scan pattern is designed to compensate for a thermallensing effect, which is an optical effect on subsequent laser pulsescaused by a temperature gradient induced by previous laser pulses. Insome embodiments, the scan pattern includes forming a plurality oflayers (or lines, or spots) in an interlaced manner such that any layersthat are immediately adjacent each other in their spatial order are notimmediately adjacent each other in the time order in which they areformed. In some embodiments, the scan pattern in the optical zone isconfigured to produce a refractive index modification profile of aFresnel lens.

This summary and the following detailed description are merelyexemplary, illustrative, and explanatory, and are not intended to limit,but to provide further explanation of the invention as claimed.Additional aspects, features, objectives and advantages of the inventionwill be set forth in the descriptions that follow, and in part willbecome apparent from the written description, taken in conjunction withthe accompanying drawings, illustrating by way of example the principlesof the invention, or may be learned by practice of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view illustrating the anterior surface of anintraocular lens according to one embodiment of the present invention.

FIG. 2 is a perspective view illustrating the posterior surface of theintraocular lens shown in FIG. 1.

FIG. 3 is a side view of a portion of the intraocular lens shown in FIG.1.

FIG. 4 is an illustration of a system for modifying the refractive indexof an acrylic material according to many embodiments of the presentinvention.

FIG. 5 is a flowchart of a method in accordance with an embodiment ofmodifying a refractive index of an acrylic material according to thepresent invention.

FIG. 6A shows an image of a change in index of refraction of an acrylicmaterial irradiated with a femtosecond material at 1 hour after exposureas a function of pulse energy and number of repeat pulse exposures.Pulse energy is increased from 0.1 μJ to 0.5 μJ for 1-5 repeats of thelaser pulses. A blue color indicates a positive index change. A redcolor indicates a negative index change. FIG. 6B represents the samesample 1 day after treatment. Note that the outlines of the squares onthe upper right stays after diffusion process and the sign of the indexmodification has changed from 1 hour to 1 day.

FIG. 7A shows an image of a change in index of refraction of an acrylicmaterial irradiated with a femtosecond material at 1 hour after exposureas a function of pulse energy and number of repeat pulse exposures. Therepetition rate is 30 kHz, with a 12 μm beam waist, 1 μm spot spacing,and a pulse energy of 2-2.5-3-3.5-4 μJ, 5 repeats. A red color indicatesa negative index change. A blue color indicates a positive index change.FIG. 7B represents the same sample 1 day after treatment. As visible onthe cross-sections the sign of the index change has changed between thetwo different time points.

FIG. 8A is a graph of index of refraction vs. pulse energy (microJoules) for a crosslinked acrylic material irradiated with a femtosecondlaser with 4 repeat laser pulses at 1 and 3 days post irradiation. Notethat the index of refraction change of the acrylic material is linearwith total energy at 3 days post irradiation.

FIG. 8B is a graph of laser pulse energy (micro Joules) vs. index ofrefraction for a crosslinked acrylic material irradiated with afemtosecond laser with 8 repeat laser pulses at 1 and 3 days postirradiation. Note that the index of refraction change of the acrylicmaterial is linear with total energy at 3 days post irradiation.

FIG. 8C is a graph of index of refraction vs. pattern repeats for anacrylic material irradiated with a femtosecond laser at 3 days postirradiation. Note that the index of refraction change of the acrylicmaterial is generally linear with the number of pattern repeats at 3days post irradiation.

FIG. 9A is a graph of laser pulse energy vs. index of refraction for acrosslinked acrylic material in water at 37° C. irradiated with afemtosecond laser with 16 repeat laser pulses at 1 and 3 days postirradiation. Note that the index of refraction change of the acrylicmaterial is linear with total energy at 3 days post irradiation.

FIG. 9B is a graph of laser pulse energy vs. index of refraction for acrosslinked acrylic material in water at 37° C. irradiated with afemtosecond laser with 8 repeat laser pulses at 1 and 3 days postirradiation. Note that the index of refraction change of the acrylicmaterial is linear with total energy at 3 days post irradiation.

FIG. 9C is a graph of pattern repeats vs. index of refraction for anacrylic material irradiated with a femtosecond laser at 3 days postirradiation. Note that the index of refraction change of the acrylicmaterial is generally linear with the number of array repeats at 3 dayspost irradiation.

FIGS. 10A and 10B show that irradiation of a crosslinked acrylicmaterial irradiated with a nanosecond laser can cause an index changecomparable to a femtosecond laser. FIG. 10A is an image of the indexchange in a crosslinked acrylic material irradiated with a 0.6 ns pulselaser, with a repetition rate of 30 kHz, a pulse energy of 6.6 uJ, ofspot size 1.5 um, with 1, 2, 4, 8 and 16 irradiation repeats.

FIG. 11 illustrates the absorption of a thin layer of an acrylicmaterial, showing both the linear (single photon) absorption coefficientand the two-photon absorption coefficient, as well as the photopicsensitivity curve of the human eye and high-lightened spectral areas inwhich a significant two photo absorption can be achieved along withminimal photopic sensitivity to the human eye.

FIG. 12 shows experimentally obtained two-photon absorption coefficientfor the acrylic material as a function of pulse energy applied to thesample for different laser wavelengths as well as glass as a referencesample for 3 photon absorption.

FIG. 13A shows measured transmission data over laser pulse average power(over pulse duration) using the acrylic material at four wavelengths andthe corresponding curve fitting matching to a two photon absorption ofthe incident laser light.

FIG. 13B shows the calculated two-photon absorption coefficient as afunction of pulse energy at the wavelengths using the measured data inFIG. 13A.

FIGS. 14A-14D illustrate the spatial distribution of pulse energyabsorption near the focus point due to multi-photon absorption in thevolume above the focus point. FIG. 14A shows a graphical representationof the absorbed energy moving towards the incident laser pulse due tothe two photon absorption. FIG. 14B shows similar simulation results ofa low and high energy laser pulse applied at the same focal depth butdue to the higher two photon absorption most of the energy of the highenergy pulse is absorbed above the laser focus. FIG. 14C shows thiseffect in a sample in which the same focal depth was irradiated in theacrylic material at different energies demonstrating the focus changetowards the incident laser. FIG. 14D shows the exposed sample crosssection with high lightened fluorescence of the lasered area.

FIG. 15 is a flow chart illustrating a refractive index modificationmethod according to an embodiment of the present invention. Correctionof the intensity dependent focus is applied.

FIG. 16 is a flow chart illustrating a refractive index modificationmethod according to an embodiment of the present invention consideringthermal lensing of the acrylic material.

FIG. 17A shows the thermal FEM modeling of an exemplary IOL with anexemplary uniform laser volume heating due to laser exposure and lightabsorption inside the lens.

FIG. 17B shows the time course of selected points within the volume ofthe eye after laser pulse irradiation in the modeling of FIG. 17A.

FIGS. 18A and 18B illustrates pre-compensation of laser beam directionto ensure a sufficiently large light distribution area on the retina inorder to reduce light intensity on the retina, according to anembodiment of the present invention.

FIG. 19 is a flow chart illustrating a refractive index modificationmethod according to an embodiment of the present invention.

FIG. 20 illustrates an exemplary index Fresnel lens formed in an IOLmaterial by refractive index modification according to an embodiment ofthe present invention.

FIG. 21 shows an example of a Fresnel refractive index profile along aradial direction according to an embodiment of the present invention.

FIGS. 22A and 22B show an example of a Fresnel lens formed in a contactlens according to an embodiment of the present invention.

FIG. 23 shows ring-shaped focus spots formed by a vortex beam accordingto an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

In many embodiments, a method of altering a refractive property of acrosslinked acrylic polymer comprises generating a light beam with alight source; and irradiating the crosslinked acrylic polymer with thelight beam, thereby producing a predetermined change in a refractiveproperty of the crosslinked acrylic polymer. Preferably, irradiationwith the laser light beam results in a change in refractive index of thecross-linked acrylic polymer, thereby causing the predetermined changein the refractive property. In some embodiments, a first change in therefractive index is negative during a first time period afterirradiation and a second change in the refractive index is positive in asecond time period after irradiation. In some embodiments, a change inrefractive index of the cross-linked acrylic polymer relative to thepre-irradiation refractive index at a location within the crosslinkedacrylic polymer is linearly related with a total energy of theirradiation with the light source.

In preferred embodiments, the light source is a pulsed laser source, andthe pulsed laser source produces at least one of femtosecond laser pulseand picosecond laser pulses. In the preferred embodiments, the pulsedlaser pulses irradiate the crosslinked acrylic polymer and produce afirst change in the refractive index is negative during a first timeperiod after irradiation and a second change in the refractive index ispositive in a second time period after irradiation. The first timeperiod may occur either before or second time period. The predeterminedchange in refractive index relative to the pre-irradiation refractiveindex at a location within the crosslinked acrylic polymer is determinedby controlling a total energy of the irradiation with the light source.

A method of altering a refractive property of an implantable intraocularlens having an optic body including an optical zone and a peripheralzone entirely surrounding the optical zone, comprises generating a lightbeam with a light source; and irradiating the optical zone with thelight beam. The optical zone comprises a crosslinked acrylic materialand irradiation with the light beam produces a predetermined change in arefractive property of the crosslinked acrylic polymer, thereby alteringa refractive property of the intraocular lens. Preferably, irradiationwith the laser light beam results in a change in refractive index of thecross-linked acrylic polymer, thereby causing the predetermined changein the refractive property. Preferably, first change in the refractiveindex is negative during a first time period after irradiation and asecond change in the refractive index is positive in a second timeperiod after irradiation. Preferably, the change in refractive indexrelative to the pre-irradiation refractive index at a location withinthe crosslinked acrylic polymer is linearly related with a total energyof the irradiation with the light source.

Preferably, the light source is a pulsed laser source. The pulsed lasersource produces femtoseconds or longer up to a few nanoseconds laserpulses. A first change in the refractive index caused by irradiationwith the pulsed laser is negative during a first time period afterirradiation and a second change in the refractive index is positive in asecond time period after irradiation. Preferably, the change inrefractive index relative to the pre-irradiation refractive index at alocation within the crosslinked acrylic polymer is linearly related witha total energy of the irradiation with the light source.

One embodiment of an intraocular lens suitable for use in connectionwith the present invention is shown in FIGS. 1-3.

As illustrated in FIGS. 1-3, an intraocular lens 10, which is preferablyfoldable, comprises an optic body 11 including an optical zone 12 and aperipheral zone 13 entirely surrounding the optical zone 12. The opticbody 11 has an anterior face 14, a substantially opposing posterior face18, an optic edge 20, and an optical axis 22. The anterior face 14comprises a central face 24, a peripheral face 28, and a recessedannular face 30 therebetween that is disposed posterior to theperipheral face 28. The intraocular lens 10 further comprises at leastone haptic 32 that is integrally formed with the peripheral zone 13. Thehaptic 32 comprises a distal posterior face 34, a proximal posteriorface 38, and a step edge 39 disposed at a boundary therebetween. Thehaptic further comprises a side edge 40 disposed between the optic edge20 and the step edge 39. The proximal posterior face 38 and theposterior face 18 of the optic body 11 form a continuous surface 48. Anedge corner 50 is formed by the intersection of the continuous surface48 with the optic edge 20, the side edge 40, and the step edge 39.

The optic body 11 is preferably generally circular having a radius Roand is typically constructed of deformable-elastic transparent lens bodyof crosslinked acrylic material having a tensile strength sufficient toresist deformation after implantation into the eye as by forces exertedby growing tissue around the IOL; a flexibility as measured byelongation at break sufficient to allow the lens body to be readilyfolded, rolled or otherwise deformed to a low profile condition forimplantation through a small incision into the eye; an elastic memorywhich enables the folded lens body to naturally and at a controlled ratereturn to its original shape and optical resolution without damaging orotherwise traumatizing eye tissue; and a low-tack surface which will notstick to surgical instruments used to hold and guide the lens bodyduring insertion and positioning within the eye.

In particular, the optic body is a crosslinked acrylic materialcomprising copolymers of methacrylate and acrylate esters which arerelatively hard when cold and relatively soft at body temperature,crosslinked with a diacrylate ester to produce a cross-linked acrylicmaterial having a substantially tack-free surface, a crosslink densitybetween 0.5×10⁻² and 1.5×10⁻² moles per liter, a glass transitiontemperature in the range of −30° to 25° C., a tensile modulus in therange of 1000 to 3000 psi and an elongation at break of between 100 and300%. Such a lens body is easily folded, rolled or otherwise deformedinto a low profile for insertion through a small incision and afterinsertion will naturally return to its original optical resolution at aslow controlled rate in between 20 and 180 seconds even if the lens bodyhas been deformed to a low profile condition for an extended period oftime. The slow return allows the surgeon adequate time to locate thefolded IOL in the eye before the lens body returns to its original shapeand resolution and insures that the unfolding of the lens will notdamage or otherwise traumatize ocular tissue. Furthermore, the opticbody of the foregoing material and composition possesses a desiredtensile strength to resist deformation in response to forces exerted bytissue growing around the implanted lens body thereby maintaining thedesired optical characteristics and resolution of the lens body.

In some embodiments, in the formation of the deformable-elastic acrylicmaterial, the copolymers of methacrylate and acrylate esters are mixedat approximately a 45 to 55 weight percent ratio and the relatively hardmethacrylate ester is a fluoroacrylate. The fluoroacrylate functions asa surface energy lowering agent as well as a monomer providing long termstable inertness and tensile strength to the polymer without adverselyeffecting the pliancy of the resulting material. In this regard, thefluoroacrylate is present in a concentration range by weight of between5 and 25% and preferably is trifluoroethyl methacrylate. Also in thepreferred formulation of the crosslinked acrylic, the mixture of thecopolymers is partially polymerized prior to chemical crosslinking withdiacrylate ester in a concentration range of between 0.5 and 3.0 percentby weight. The polymer may incorporate an ultraviolet (UV) lightblocking additive, preferably a permanent (chemically bound) ultraviolet(UV) light-blocking additive known in the art, such as2-(4-benzoyl-3-hydroxyphenoxy) ethyl acrylate.

The resulting crosslinked acrylic material may be molded and formed intolens bodies machined to have the desired optical characteristics andresolution with haptics extending therefrom either integral with orseparately attached to the lens body.

In a preferred embodiment, the optic body 11 is made of SENSAR® IOLbrand of hydrophobic acrylic IOL material.

Although the crosslinked acrylic material described herein is describedprimarily for use in an optic body, the crosslinked acrylic material maybe used in other applications wherein a change of refractive index isdesired.

The optic body 11 material is preferably selected such that the opticalzone 12 is optically clear and exhibits biocompatibility in theenvironment of the eye. Selection parameters for suitable lens materialsare well known to those of skill in the art. See, for example, David J.Apple, et al., Intraocular Lenses. Evolution, Design, Complications, andPathology, (1989) William & Wilkins. Foldable/deformable materials areparticularly advantageous since optics made from such deformablematerials may be rolled, folded or otherwise deformed and inserted intothe eye through a small incision. The lens material before irradiationpreferably has a refractive index allowing a relatively thin, andpreferably flexible optic section, for example, having a centerthickness in the range of about 150 microns to about 1000 microns,depending on the material and the optical power of the optic body 11.For example, in one embodiment, the optic body 11 is made of SENSAR® IOLbrand of acrylic material, an optically clear, hydrophobic, acrylicelastomer with an optical power of 20D. IOLS made of the compositioncontained in the SENSAR® IOL brand are described in commonly-owned U.S.Pat. No. 4,834,750, which is incorporated here by reference. In such anexemplary embodiment, the optical zone 12 has a center thickness Tc thatis preferably in the range of about 0.5 mm or less to about 1.0 mm ormore, more preferably between about 0.7 mm and 0.9 mm. The centerthickness Tc may vary from these ranges depending on factors such as thelens material and the dioptric power of the optical zone 12. The opticbody 11 preferably has a diameter of at least about 4 mm to about 7 mmor more, more preferably about 5 mm to about 6.5 mm or about 6.0 mm. Asused herein the term “thickness” generally refers to a dimension of aportion or feature of the intraocular lens 10 as measured substantiallyalong the optical axis 22.

The intraocular lens 10 may comprise any of the various means availablein the art for centering or otherwise locating the optical zone 12within the eye. For example, as illustrated in FIGS. 1-3, theintraocular lens 10 may comprise one or more fixation members or haptics32. The haptics 32 are preferably integrally made of the same materialas the optic body 11 so as to form a one-piece IOL. Alternatively, thehaptics 32 may be integrally formed in a common mold with the optic body11, but be made of a different material than the optic body 11. In otherinstances, the haptics 32 formed of the same material as the optic body11, but haptics 32 and the optic body 11 materials have differentstates, for instance differing amounts of water content or percentage ofcross-linked polymer. In yet other embodiments, the haptics may beformed separately from the optic body 11 and attached to the optic body11 to provide a three-piece configuration. In such configurations, thehaptics 32 may comprise any of a variety of materials which exhibitsufficient supporting strength and resilience, and which aresubstantially biologically inert in the intended in vivo or in-the-eyeenvironment. Suitable materials for this purpose include, for example,polymeric materials such as polypropylene, PMMA, polycarbonates,polyamides, polyimides, polyacrylates, 2-hydroxymethylmethacrylate, poly(vinylidene fluoride), polytetrafluoroethylene and the like; and metalssuch as stainless steel, platinum, titanium, tantalum, shape-memoryalloys, e.g., nitinol, and the like. In other embodiments, theintraocular lens 10 comprises a positioning means that allows the opticbody 11 to move along the optical axis 22 or be deformed in response todeformation of the capsular bag and/or in response to the ciliarymuscles of the eye.

The optical zone 12 may take any of the forms known in the art. Forexample the optical zone 12 may be biconvex, plano-convex,plano-concave, meniscus, or the like. The optical power of the opticalzone 12 may be either positive or negative. The general profile or shapeof the posterior face 18 and the central face 24 of the optic zone 12may be any used for producing an optic based on refraction of incidentlight. For instance, the posterior face 18, the central face 24, or bothfaces 18, 24 may be spherical with an overall radius of curvature thatis either positive or negative. Alternatively, the profile or shape ofeither the posterior face 18, the central face 24, or both faces 18, 24may be parabolic or any aspheric shape common in the art for reducingaberrations such as spherical aberrations. For example, the posteriorface 18 or the central face 24 may be an aspheric surface designed toreduce spherical aberrations based on either an individual cornea orgroup of corneas as described by Piers et al. in U.S. Pat. No. 6,609,673and U.S. patent application Ser. Nos. 10/119,954, 10/724,852, hereinincorporated by reference. Other aspheric and asymmetric surfaceprofiles of the posterior face 18 or the central face 24 of use withinthe art are also consistent with embodiments of the intraocular lens 10.The posterior face 18 or the central face 24 may alternatively beconfigured to provide more than one focus, for example to correct forboth near and distant vision as described by Portney in U.S. Pat. No.4,898,461.

The optical zone 12 may take any of the forms known in the art. Forexample the optical zone 12 may be biconvex, plano-convex,plano-concave, meniscus, or the like. The optical power of the opticalzone 12 may be either positive or negative. The general profile or shapeof the posterior face 18 and the central face 24 of the optic zone 12may be any used for producing an optic based on refraction of incidentlight. For instance, the posterior face 18, the central face 24, or bothfaces 18, 24 may be spherical with an overall radius of curvature thatis either positive or negative. Alternatively, the profile or shape ofeither the posterior face 18, the central face 24, or both faces 18, 24may be parabolic or any aspheric shape common in the art for reducingaberrations such as spherical aberrations. For example, the posteriorface 18 or the central face 24 may be an aspheric surface designed toreduce spherical aberrations based on either an individual cornea orgroup of corneas as described by Piers et al. in U.S. Pat. No. 6,609,673and U.S. patent application Ser. Nos. 10/119,954, 10/724,852, hereinincorporated by reference. Other aspheric and asymmetric surfaceprofiles of the posterior face 18 or the central face 24 of use withinthe art are also consistent with embodiments of the intraocular lens 10.The posterior face 18 or the central face 24 may alternatively beconfigured to provide more than one focus, for example to correct forboth near and distant vision as described by Portney in U.S. Pat. No.4,898,461.

At least portions of the posterior face 18, the central face 24, or bothfaces 18, 24 of the optical zone 12 may comprise one or more opticalphase plates. In such embodiments, the total optical power of theoptical zone 12 is a combination of the refractive power of theposterior face 18 and the central face 24, and the optical power of theone or more diffraction orders produced by the one or more phase plates.The one or more phase plates may be either a monofocal phase plateproviding one dominant diffraction order or a multifocal phase plate,such as a bifocal phase plate, for providing, for instance, simultaneousnear and distant vision. Other types of phase plates may also be used.For example, the phase plate may be based on a change in the refractiveindex of the material used to form the optical zone 12.

The total optical power of the optical zone 12 is preferably within arange of at least about +2 Diopters to about +50 Diopters or more, morepreferably within a range of about +5 Diopters to about +40 Diopters,and most preferably a range of about +5 Diopters to about +30 Diopters.The total optical power may be either positive or negative, for instancewithin a range of about −15 Diopters or less to about +15 Diopters ormore, or within a range of about −10 Diopters to about +10 Diopters.Other ranges of refractive optical power may be preferred, depending onthe particular application and type of intraocular lens to be used.

In certain embodiments, the haptics 32 are characterized by a hapticthickness Th that is equal to a distance, as measured along the opticalaxis 22, between the distal posterior face 34 of the haptic 32 and thesubstantially opposing anterior face 58. Preferably, the hapticthickness Th is greater than or approximately equal to an optic edgethickness To, as measured along the optical axis 22. The thicknesses Thand To may be selected based on the particular material from which theintraocular lens 10 is made, the amount of rigidity desired, the opticalpower of the lens 10, and other such factors. In one embodiment, atleast one of the haptic thickness The optic edge thickness To, isbetween at least about 0.4 mm to about 0.5 mm or more.

As a result of the step edge 39, the distal posterior face 34 of eachhaptics 32 has an anterior offset relative to the proximal posteriorface 38. In certain embodiments, the step edge 39 has a thickness H thatis much less than the optic edge thickness To. For example, the stepedge thickness H is about 0.1 mm and the optic edge thickness To isbetween about 0.4 mm or less and about 0.5 mm or more. Alternatively, inother embodiments, the step edge thickness H is greater than orapproximately equal to the optic edge thickness To. The step edgethickness H may be selected based on various design parameters,including, the particular material from which the intraocular lens 10 ismade, the amount of rigidity desired in the haptics 32, and other suchfactors. Preferably, step edge thickness H is selected sufficientlylarge so that the integrity of the contact of the edge corner 50 withthe posterior capsule of the eye is maintained so as to help avoid PCO.

In certain embodiments, at least a portion of the step edge 39 is astraight line and is substantially disposed at a radius R1 from theoptical axis 22. Alternatively or additionally, at least a portion ofthe step edge 39 may be arcuate in shape. The radius R1 isadvantageously greater than the radius Ro of the optic edge 20 so that aproximal portion of the haptic 32 forms a buttress 51 that is preferablythicker than a distal portion 52 of the haptic 32 and the edge thicknessTo. The buttress 51 of each haptic 32 provides greater haptic rigidityin the vicinity of the peripheral zone 13, resulting in a biasing forcethat biases the distal portion 52 of the haptic 32 away from the opticalzone 12. The biasing force away from the optical zone 12 can favorablyact to reduce the tendency of the haptics 32 to stick to the opticalzone 12. Such sticking problems have been noted with certain one-pieceIOL materials that are both soft and tacky. Another potential benefit ofthe step edge 39 is that the thickness of the distal portion 52 of eachhaptic 32 Th may be fabricated to be less than the thickness of thebuttress 51, thus reducing the total volume of the intraocular lens 10and permitting a smaller incision in the eye to be used during surgery.The greater haptic rigidity in the vicinity of the peripheral zone 13 ofthe optic body 11 also results in a radial force for centering theintraocular lens 10 within the eye and provides an axial force, asexplained below herein. The axial force pushes the edge corner 50 thatsurrounds the posterior face 18 against the posterior capsule of the eyeto help prevent PCO. Disposing the step edge 39 at a radius R1 that isgreater than Ro provides yet another potential advantage. The greaterrigidity provided by the buttress 51 permits the creation of a flexpoint Wf near the peripheral zone 13 that allows the haptic 32 to flexin a plane perpendicular to the optical axis 22 while maintainingoverall rigidity in the vicinity of W_(f). As illustrated in FIG. 2, thewidth of the haptic 32 in the vicinity of the flex point W_(f) is lessthan the haptic thickness in the vicinity of the flex point W_(f). Thus,the haptic 32 may flex more in a plane perpendicular to the optical axis22 than in a plane parallel to the optical axis 22.

In certain embodiments, the peripheral zone 13 is substantially formedby the peripheral face 28, the optic edge 20, and the peripheral portionof the posterior face 18. As illustrated in FIG. 1, the peripheral zone13 and the buttress 51 form generally rigid structures, the rigidity ofthe buttress 51 being due, at least in part, to the favorable locationof the step edge 39 at the radius R1, on the haptic 32. The location ofstep edge 39 at a radius R1>R0 in combination with the rigidity of theperipheral zone 13 allows the central face 24 to be recessed such thatthe recessed annular face 30 of the peripheral zone 13 is posterior tothe peripheral face 28. This recessed configuration of the central face24, compared to an optic not having the recessed annular face 30,advantageously reduces the total volume of the intraocular lens 10 byreducing the overall thickness of the optical zone 12. Alternatively,the central face 24 is not recessed, thus increasing the overallrigidity of the intraocular lens 10, but also increasing the totalvolume of the lens.

As illustrated in FIG. 3, in certain embodiments, the distal posteriorface 34 of each haptic 32 is perpendicular to the optical axis 22. Inother embodiments, the haptic 32 further comprises an anterior face 58that is also substantially perpendicular to the optical axis. In suchembodiments, the step edge 39 produces an offset relationship betweenthe distal portion 52 of the haptics 32 and the peripheral zone 13. Thisoffset relationship may be favorably used to convert the radial force ofthe ciliary muscles of the eye on the haptics 32 into an axial forcethat biases or pushes the posterior face 18 of the optic body 11 in aposterior direction along the optical axis 22 and against the posteriorcapsule of the eye. This is accomplished without the need for angledhaptics, which can be more difficult and/or expensive to manufacturethan when the distal posterior face 34, the anterior face 58, or boththe distal posterior face 34 and the anterior face 58 are manufacturedsubstantially perpendicular to the optical axis. Alternatively, thehaptics 32 may be manufactured such that the distal posterior face 34and/or the anterior face 58 are disposed at an angle relative to a planeperpendicular to the optical axis 22. This configuration may be used toincrease the amount of posterior bias or force on the posterior face 18of the optic body 11 against the posterior capsule. In suchconfiguration the angle is preferably between about 2 degrees or lessand at least about 12 degrees.

In many embodiments, the index of refraction of the acrylic material isachieved by irradiation of the acrylic material with a suitable lightsource. In many embodiments, the light source is a pulsed laser.

The present invention can be implemented by a system 200 that projectsor scans an optical beam into a patient's eye 201 containing the optic10, such as the system shown in FIG. 4. The system 200 includes controlelectronics 210, a light source 220, an attenuator 230, a beam expander240, focusing lens' 250, 260 and reflection means 270. Controlelectronics 210 may be a computer, microcontroller, etc. Scanning may beachieved by using one or more moveable optical elements (e.g. lenses250, 260, reflection means 270) which also may be controlled by controlelectronics 210, via input and output devices (not shown). Another meansof scanning might be enabled by an electro optical deflector device(single axis or dual axis) in the optical path. Although FIG. 4 showsthe optical beam directed to a patient's eye, it should be understoodthat the intraocular lens may be irradiated before placement into thepatient's eye in order to customize a refractive property of theintraocular lens.

During operation, the light source 220 generates an optical beam 225whereby reflection means 270 may be tilted to deviate the optical beam225 and direct beam 225 towards the patient's eye 201 and particularlyinto the crosslinked acrylic polymer in order to alter the refractiveindex of said polymeric acrylic. Focusing lens' 250, 260 can be used tofocus the optical beam 225 into the patient's eye 201. The positioningand character of optical beam 225 and/or the scan pattern it forms onthe eye 201 may be further controlled by use of an input device such asa joystick, or any other appropriate user input device.

Although not shown in FIG. 4, the laser system 200 preferably alsoincludes imaging and visualization sub-systems, such as and withoutlimitation, an optical coherence tomography (OCT) system, a videomonitoring system, etc. These sub-systems are used to provide images ofand to locate the various anatomical structures of the eye as well asthe IOL, which can assist in performance of the various methodsdescribed later in this disclosure. Many types of imaging andvisualization sub-systems are known in the art and their detaileddescriptions are omitted here. For example, commonly owned U.S. Pat. No.8,845,625, which is incorporated herein by reference in its entirely,discloses in its FIGS. 1-4 and accompanying descriptions in thespecification, an ophthalmic laser surgical system that includes anultrafast laser source, a beam delivery optical system includingscanning devices, an OCT system, an imaging system for viewing an imageof the eye, an aim beam system, and related control system.

The selected light source is not particularly limited so long as theemitted radiation is capable of modifying the refractive index of thecrosslinked acrylic material in the manner desired. In many embodiments,the selected light source is a laser, and more particularly a pulsedlaser source.

In many embodiments, the light source is a 320 nm to 800 nm pulsed lasersource. In many embodiments, the light source 220 is a 320 nm to 800 nmlaser source such as an tunable femtosecond laser system or it may be aNd:YAG laser source operating at the 2nd harmonic wavelength, 532 nm, or3rd harmonic wavelength, 355 nm. Other options are frequency double ortripled femtosecond laser sources which emissions fall in this spectralband. One limit of the suitable wavelengths is the transmission of thecornea. The transmission of the cornea at 355 nm is about 85% and startsto strongly drop off at 320 nm (50% transmission) to 300 nm with about2% transmission whereas the lens absorption is approximately 99%. Also,for older people, light scattering of the cornea is minimal while lightscattering of the lens has considerably increased (cataract). Importantto the wavelength selection is that the crosslinked acrylic polymershows multi-photon (two or three photo for example) absorption at theused laser wavelength and the laser wavelength itself is not linearlyabsorbed by the material.

In operation, the light of the light source is focused and is scanned inthe crosslinked acrylic polymer in order to effect a change of therefractive index in a volume of the crosslinked acrylic polymer. Theshape and volume of the volume whose refractive index is changed isdetermined by the change in the refractive property of the intraocularlens that is desired. The shape of the volume effected by theirradiation with the light source is not particularly limited. Forinstance, the volume may be lens shaped, biconvex, plano-convex,plano-concave, meniscus, or the like, disc shaped, parabolic or theirwave-stepped Fresnel-type combination thereof—or in any other3-dimensional shape suitable to cause the desired change in refractiveproperty of the intraocular lens.

Where a pulsed laser source is used, the focused pulsed laser source isswept in an array of laser pulses having a predetermined spot size andspot spacing. The array of laser pulses may be repeated in the samepattern a predetermined number of times such that substantially the samelocations within the crosslinked acrylic polymer are irradiated apredetermined number of times. These array repeats may be accomplishedby sweeping the laser source such that all the predetermined repeats areirradiated at a first laser position before laser source is moved to asecond position in the crosslinked acrylic polymer. These repeats canalso just be shifted to a slightly different depth in order to affectrelative untreated volume but with the same pattern. Single lay depthdifference may be in the order of 1 to 200 um more preferred 2 to 15 um.Alternatively, the array repeats may be accomplished by completing afirst sweep of the array with the pulsed laser beam and depositing onepulse at each array position and then repeating the array sweep forsubsequent repeat. Preferably, the crosslinked acrylic polymer absorbsat least a portion of the laser radiation.

The pulse energy of laser pulses is generally between 0.01 μJ and 50 μJ.In many embodiments, the pulse energy will be between 0.05 μJ and 20 μJ,or more precisely, between 0.1 μJ and 0.7 μJ, or between 0.05 μJ and 1μJ.

A pulse repetition rate of the laser pulses is generally between 1 kHzand 10 MHz. In many embodiments, the pulse repetition rate is between100 kHz to 600 kHz, or between 1 KHz to 80 KHz.

Spot sizes of the laser pulses are generally smaller than 20 μm. In manyembodiments, the spot size is preferably smaller than 15 μm, typically0.5 μm to 3 μm. In some embodiments, the spot size is in the range of 10μm to 15 μm.

When a pulsed laser source is used, a pulse duration of the laser pulsesis generally between 0.1 ps and 10 ns. For purposes of this application,femtosecond laser pulses are generally referred to as pulsed durationsfrom 100 fs to 500 fs, and nanosecond laser pulses are defined as laserpulses from 0.5 ns to 10 ns. FIGS. 10A and 10B show that irradiation ofa crosslinked acrylic material irradiated with a nanosecond laser cancause an index change comparable to a femtosecond laser. FIG. 10A is animage of the index change in a crosslinked acrylic material irradiatedwith a 0.6 ns pulse laser, with a repetition rate of 30 kHz, a pulseenergy of 6.6 μJ, a spot size 1.5 μm, with 1, 2, 4, 8 and 16 irradiationrepeats. This has approximately the same index change as when thecrosslinked acrylic material is irradiated with a 0.6 ps pulse laser,with a repetition rate of 30 kHz, a pulse energy of 1 μJ, a spot size1.5 μm, with 1, 2, 4, 8 and 10 irradiation repeats. Both cases result ina maximum change of the index of refraction of 0.25 lambda.

A numerical aperture should be selected that preferably provides for thefocal spot of the laser beam to be scanned over a scan range of 6 mm to10 mm in a direction lateral to a Z-axis that is aligned with the laserbeam. The NA of the system should be less than 0.6, preferably less than0.5 and more preferably in a range of 0.01 to 0.4, typically between0.03 and 0.3. In some specific embodiments, the NA is 0.15. In afemtosecond laser system, the NA is 0.02 to 0.09 with wavelength being705 nm.

FIG. 5 shows a flowchart of a method in accordance with an embodiment ofthe present invention. A first step 301 involves generating a beam oflight from a 320 nm to 800 nm laser system. A next step 302 involvestranslating and focusing the beam of light within the eye in acontrolled fashion so as to be incident on the acrylic material insidesaid eye in order to modify the refractive index of said material tomodify the refractive state.

Irradiation with the light beam as described herein results in a changein refractive index of the cross-linked acrylic polymer, thereby causingthe predetermined change in the refractive property of the intraocularlens. Applicants have determined that the crosslinked acrylic polymersexhibit both positive and negative changes in the refractive index ofthe material after irradiation with the laser light source. That is, thecrosslinked acrylic materials exhibit a first change in the refractiveindex that is negative during a first time period after irradiation anda second change in the refractive index that is positive in a secondtime period after irradiation. The first time period may precede thesecond time period or may occur after the second time period. That is,in the crosslinked acrylic material, there is both a positive andnegative index change after irradiation, and both the negative andpositive changes in the index of refraction contribute to the resulting(i.e. final) index of refraction of the irradiated material.

It should be emphasized that different IOL materials respond to laserirradiation differently in terms of the sign and magnitude of therefractive index change or the time course of the change. The behaviorof each material may be understood through experimentation. Somespecific examples are described below, and it should be noted that theprinciple and methods described below may be applied to other IOLmaterials with suitable modifications.

Without being limited by theory, one effect of the laser irradiation isto change the hydrophobicity of the acrylic material. As a result, wateris expelled from the area in or around the area that has beenirradiated, which causes or may cause a positive change in therefractive index. Another effect of the laser irradiation is to causelocal heating portion of the crosslinked acrylic polymer irradiated withthe laser pulses, which causes or may cause a negative index change inthe material. Also, also changes the hydrophobicity, which causes apositive index change. The index change typically is proportional tototal energy.

This feature of having both a positive and negative index change isillustrated in FIGS. 6 and 7. FIG. 6A shows an image of a change inindex of refraction of an acrylic material irradiated with a femtosecondmaterial at 1 hour after exposure as a function of pulse energy andnumber of repeat pulse exposures. Pulse energy is increased from 0.1 μJto 0.5 μJ for 1-5 repeats of the laser pulses. A blue color indicates apositive index change. A red color indicates a negative index change.FIG. 6B represents the same sample 1 day after treatment. Note that theoutlines of the squares on the upper right stays after diffusion processand the sign of the index modification has changed from 1 hour to 1 day.

FIG. 7A shows an image of a change in index of refraction of an acrylicmaterial irradiated with a femtosecond material at 1 hour after exposureas a function of pulse energy and number of repeat pulse exposures. Therepetition rate is 30 kHz, with a 12 μm beam waist, 1 μm spot spacing,and a pulse energy of 2-2.5-3-3.5-4 μJ, 5 repeats. A red color indicatesa negative index change. A blue color indicates a positive index change.FIG. 7B represents the same sample 1 day after treatment. As visible onthe cross-sections the sign of the index change has changed between thetwo different time points.

Following completion of the positive and negative index changes, theirradiated volume of the crosslinked acrylic material reaches a finalequilibrium state characterized by an index of refraction that isdifferent from the index of refraction of the crosslinked acrylicpolymer in its pre-irradiated state and different from the index ofrefraction of the of the crosslinked acrylic material that has not beenirradiated. That is, the change in refractive index relative to thepre-irradiation refractive index (or relative to the index of therefraction of the non-irradiated portion of the lens) in the crosslinkedacrylic polymer is proportion to a total energy of the irradiation withthe light source at each location. In preferred embodiments, the changein refractive index relative to the pre-irradiation refractive index (orrelative to the index of the refraction of the non-irradiated portion ofthe lens) in the crosslinked acrylic polymer is linearly proportional toa total energy of the irradiation with the light source at eachlocation.

This feature is shown, for instance, in FIGS. 8 and 9. FIG. 8A is agraph of index of refraction vs pulse energy (micro Joules) for acrosslinked acrylic material irradiated with a femtosecond laser with 4repeat laser pulses at 1 and 3 days post irradiation. Note that theindex of refraction change of the acrylic material is linear with totalenergy at 3 days post irradiation. FIG. 8B is a graph of laser pulseenergy (micro Joules) vs. index of refraction for a crosslinked acrylicmaterial irradiated with a femtosecond laser with 8 repeat laser pulsesat 1 and 3 days post irradiation. Note that the index of refractionchange of the acrylic material is linear with total energy at 3 dayspost irradiation. FIG. 8C is a graph of index of refraction vs. patternrepeats for an acrylic material irradiated with a femtosecond laser at 3days post irradiation. Note that the index of refraction change of theacrylic material is generally linear with the number of pattern repeatsat 3 days post irradiation.

FIG. 9A is a graph of laser pulse energy vs. index of refraction for acrosslinked acrylic material in water at 37° C. irradiated with afemtosecond laser with 16 repeat laser pulses at 1 and 3 days postirradiation. Note that the index of refraction change of the acrylicmaterial is linear with total energy at 3 days post irradiation. FIG. 9Bis a graph of laser pulse energy vs. index of refraction for acrosslinked acrylic material in water at 37° C. irradiated with afemtosecond laser with 8 repeat laser pulses at 1 and 3 days postirradiation. Note that the index of refraction change of the acrylicmaterial is linear with total energy at 3 days post irradiation. FIG. 9Cis a graph of pattern repeats vs. index of refraction for an acrylicmaterial irradiated with a femtosecond laser at 3 days post irradiation.Note that the index of refraction change of the acrylic material isgenerally linear with the number of array repeats at 3 days postirradiation.

It should be noted that for some other IOL materials, the change inrefractive index at each location due to laser irradiation may change ina non-linear manner with respect to the total energy of the irradiation.The behavior of each IOL material may be understood throughexperimentation.

U.S. Pat. Nos. 4,834,750 and 7,615,073 and U.S. Patent Publication2015/0335477 are incorporated herein by reference in their entirety.

Refractive Index Modification Through Localized Heating UsingMulti-Photon Absorption

Modification of refractive index of the intraocular lens may be achievedby directly altering the chemical bonds of the crosslinked acrylicmaterial of the lens through multi-photon absorption. To directly alterthe chemical bonds, photon energy of >5 eV is needed, which requirestwo- or three-photon absorption in the visible wavelength range. Oneproblem with this approach is that most IOL materials are specificallymade to be very resistant to chemical changes, as they are designed andmanufacture to be inert and fully cured prior to implantation and shouldnot react to anything once implanted. In the embodiments describedbelow, instead of changing the chemical bonds to alter the chemicalstructure of the IOL material, a pulsed laser beam is used to locallyalter the refractive index of the IOL material by means of localizedheating. Further, the wavelength and power density of the pulse laserbeam are selected to induce multiphoton absorption of the laser light.In other words, the laser energy is absorbed by the IOL material throughmultiphoton absorption, and majority of the absorbed energy is releasedas heat to heat the IOL material locally to alter its refractive indexlocally.

In some embodiments, the laser light used for refractive indexmodification is in either the UV/blue spectral range (e.g. 400-450 nm)or the far red/NIR spectral range (e.g. 650-800 nm), and multi-photonabsorption allows for photons in these spectral ranges to be absorbed bythe IOL material with relatively high absorption rate. These twowavelength ranges are preferred as they are in ranges of low humanretinal sensitivity, compared to the green spectral range which has thehighest sensitivity. Low spectral sensitivity therefore allows goodpatient compliance.

The upper panel of FIG. 11 illustrates the absorption of a thin sampleof exemplary acrylic material (the SENSAR® IOL brand acrylic), showingboth the linear (single photon) absorption coefficient and thetwo-photon absorption coefficient (both in units of per micrometer layerthickness). The linear absorption coefficient has strong absorption inthe UV spectral range, up to about 365 nm, and then becomes transparentstarting at about 390 nm. The two-photon absorption spectrum, whichcorresponds to the linear absorption curve but at doubled wavelength,reaches the NIR range. The lower panel of FIG. 11 illustrates thephotopic sensitivity curve of the human eye. It can be seen that in thetwo spectral ranges mentioned above, namely the UV/blue range (e.g.400-450 nm) and the far red/NIR range (e.g. 650-800 nm), the photopicsensitivity of the eye is relatively low, while the two-photonabsorption is still sufficiently high. This make the two-photonabsorption treatment process applicable without damaging the retina ofthe patient with the treatment light. This ensures good patientcooperation during the exposure. If one uses light at the peak spectralsensitivity one can expect adverse reactions of patients as unused lightis transmitted to the retina In particular, in the far red and NIRspectral range, the light does not cause photochemical reaction on theretina, so only thermal safety limit for the retina needs to be met.

The direct linear absorption in the blue/UV spectral range may also beused. In this range, however, the photochemical effect on the retina maybe a concern, and the treatment must meet the retinal safety limit(which is a very low dosage). Additionally, the limited cornealtransmission in this spectral range due to increased light scattering inthe aged cornea of the target population may also reduce theeffectiveness of such an approach.

While one specific example of IOL material is given above, different IOLmaterials with different single photon UV absorption characteristic maychange the usable spectral range due to the specific cut-off wavelengthsof their UV/blue absorbance. For yellow dyed IOL materials, this rangecan significantly shift into the red spectral region or into the near IRrange. Further, specific resonant dye absorbers, which have narrowabsorption peaks tailored to specific laser wavelengths, may beintroduced into the IOL material. If the bandwidth is narrow enough, itmay be used even in the visible spectral range as only little energy isabsorbed. Dyes which are specifically only sensitive for two-photonabsorption may also be used.

The two-photon absorption coefficient of the IOL material may be derivedexperimentally. FIG. 12 shows experimentally obtained two-photonabsorption coefficient (a/I) for the SENSAR® IOL brand of acrylicmaterial as a function of pulse energy applied to the sample, fordifferent laser wavelengths in the NIR range. As shown in FIG. 12, atwavelengths of 700 nm, 735 nm, 750 nm, and 762 nm, the absorptioncoefficient starts to increase rapidly at certain pulse energy and thenreaches a plateau, indicating a stable two-photon absorption behavior.As a reference, the two-photon absorption coefficient of glass at 700 nmis also shown, but in the pulse energy range shown, it rises linearlywith energy but never reaches a plateau with a stable 2 photonabsorption, which indicates a three-photon absorption behavior.

The two-photon absorption coefficient as a function of the pulse energymay be obtained by measuring the transmission rate of the light throughthe sample as a function of pulse energy, then fitting two constants(threshold and coefficient) to the measured transmission rate data. Inone particular example, the equation used for the curve fitting is asfollows:

$T = {\frac{\pi\; w_{0}^{2}}{2{BP}_{m}}{\log\left\lbrack {1 + \frac{2P_{m}B}{\pi\; w_{0}^{2}}} \right\rbrack}}$

Where P_(m) is the incident power on the material, w₀ is the gaussianbeam waist radius, and:

$B = {z_{R}{\beta\left\lbrack {{{Arctan}\left( \frac{z - z_{0}}{z\; R} \right)} - {{Arctan}\left( \frac{z_{m} - z_{0}}{z\; R} \right)}} \right\rbrack}}$

Where zR is the Rayleigh range, z₀ is the beam waist location, z is thelocation of bottom of material, z_(m) is location of the top of thematerial, and β is the TPA coefficient which has two fit parametersP_(th) and P_(width) as given below:

${\beta(P)} = {\beta_{0}\left( {\frac{1}{2} + {\frac{1}{\pi}{{Arctan}\left( \frac{P_{m} - P_{th}}{P_{width}} \right)}}} \right)}$

FIG. 13A shows measured transmission data using the SENSAR® IOL brand ofacrylic material at four wavelengths, 450 nm, 515 nm, 702 nm and 740 nm,and the corresponding curve fitting matching to a two photon absorptionof the incident laser light, and FIG. 13B shows the calculatedtwo-photon absorption coefficient as a function of pulse energy at thesewavelengths. Note that in FIGS. 13A and 13B, the pulse energy has beenconverted to pulse average power.

As mentioned earlier, certain chromophores may be added to the IOLmaterial to absorb other laser wavelengths to induce two-photonabsorption and the associated heating. For example, a UV-blocking IOLmaterial, containing a UV filter, such as the TECNIS® OptiBlue IOL,which has relatively high absorption for blue light, can be altered witha 780 nm short pulsed laser as it still has significant absorption at390 nm, while the non-UV-blocking IOL material, such as the SENSAR® IOLis already in the transition zone for this wavelength. It is alsopossible to use wavelength specific absorbers for 515 nm light which maythen allow the use of 1030 nm lasers light which are non-visible for thepatients. The TECNIS® OptiBlue IOL is described in commonly-owned U.S.Pat. No. 7,278,737, which is incorporated herein by reference.

One effect of two-photon absorption is the self-limitation of the lasereffect on the material at the focus spot. Such self-limitation is causedby the light of the laser pulse being absorbed and even depleted shortlybefore it reaches the intended focus spot due to the onset of two photonabsorption in the volume in front of the focus, as the power densitybecomes sufficiently high in that volume due to focusing and exceeds thethreshold of two-photon absorption. FIG. 14A schematically illustratesthe effect that at higher pulse energies, the laser light is absorbedfurther up the focal volume, i.e. closer to the incident laser light.FIG. 14B shows numerical simulations of the absorbed energy distributionof the laser light within the SENSAR® IOL material using the measuredtwo-photon absorption coefficient, showing the simulated energyabsorption at 20 nJ (left) and 2 uJ (right). It can be seen that thespatial distribution of pulse energy absorption is shifted towards theincident laser (from the top) and very little energy is deposited in themuch smaller intended focal volume. This effect has also been confirmedexperimentally using cross-sectional phase contrast imaging andfluorescence imaging. FIG. 14C is a cross-sectional phase contrast imageshowing vertical lines of index changes generated in a SENSAR® IOLmaterial at different laser pulse energies but uniform focal depth. FIG.14D are fluorescence images of the cross-section of the material showingthe autofluorescence from the material during laser irradiations, whichis indicative of the amount of energy absorbed. Both figures show thatthe areas of index change or light absorption for lower energy pulsesare deeper in the material while the those for higher pulse energyshifted upwards, closer to the incoming laser pulses.

This self-limitation effect can prevent plasma formation and theassociated damage of the IOL material due to high power density at theintended focus spot. Thus, higher pulse energy may be used withoutdamaging the IOL material. In other words, this effect intrinsicallyincreases the dynamic range of the desired effect without causingoptical breakdown in the laser focus and damage of the sample. On theother hand, the variable depth effect, i.e. the change in absorptiondepth with pulse energy, means that the laser pulse irradiation patternshould be designed to take this effect into account, so that the actualabsorption depth occurs at intended depths. In practice (see FIG. 15),for a given lens material and given laser system parameters (e.g. thefocal distance and the numerical aperture of the system), the shift inabsorption depth due to multiphoton absorption at given pulse energiescan be obtained (step S151), for example, by numerical simulation orexperimental observation as mentioned above. Then, an initial laserpulse scan pattern, which has been designed to produce a definedrefractive index modification profile in the IOL (step S152), ismodified by moving the designed depth of each focus spot to a deeperlocation based on the shift obtained in step S151 (step S153). When thepulsed laser beam is scanned according to the modified scan pattern(step S154), the resulting refractive index modification pattern will bethe same as the defined pattern designed in step S152.

In addition to a Gaussian beam profile, other beam profiles may be used,such as a top hat shaped beam (where the light intensity profile is flatin a center region), a vortex beam (where the light intensity peaks atradial positions away from the beam center), etc. For example, spatialpulse shaping using vortex beams can be utilized to optimize the inducedlaser efficacy while increasing the threshold for material damage as thethreshold for plasma formation is hard to reach under these conditions.A vortex beam can form a ring shaped focus spot in the material, whichcan result in a more spatially even distribution of energy as comparedto a beam profile that peaks at the beam center. FIG. 23 showsring-shaped focus spots formed by a vortex beam in a SENSAR® IOLmaterial; the pulse energy was 1.5 uJ and the spot spacing was 15 μm.

Another factor that generates a self-limiting effect during laserprocessing of the IOL material is thermal lensing. Thermal lensing in anoptical medium is induced by temperature gradient in the medium, whichchanges the refractive index of the material and causes bending of thelight. The effect is temporary, and disappears when the temperaturegradient disappears due to heat diffusion. When processing the IOLmaterial using a laser beam, when the pulse repetition rate issufficiently high and the focus spots of successive pulses are locatedsufficiently close to each other in space, the focusing of thesubsequent pulses may be affected by the thermal lensing effect due tothe heat generated by previous laser pulses. The induced thermal lensingmay limit the formation of a good laser focus spot, i.e., it may defocusthe laser beam.

The magnitude of the thermal lensing effect for a given material may beestimated by numerical simulation. In methods described below that takethermal lensing effect into consideration, simulation results may beused to determine, for a given set of parameters, whether the effect ofthermal lensing is desirable/undesirable or acceptable/unacceptable, orto optimize various parameters, depending on practical requirements.

Generally speaking, if defocusing of the laser beam is to be avoided,the successive laser spots in a scan pattern should be placed outside ofthe thermal impact zone of the previous pulses. On the other hand, thedefocusing reduces the energy density at the focus spot, which maybeneficially avoid plasma formation at the focus spot and the resultingdamage of the lens material. As a result of the defocusing, a muchhigher average power of the laser beam may be used without causingplasma formation and damage to the IOL material. Thus, in someembodiments, the laser parameters (such as pulse energy, pulserepetition rate, etc.) and the scan pattern (such as the spot spacingbetween adjacent laser spots) are designed such that a thermal lensingeffect is induced in the IOL material to cause subsequent laser pulsesto be defocused. When such a technique is used, a laser beam of higheraverage power may be used without damaging the IOL material.

Another method that takes thermal lensing effect into consideration isinterlaced scan patterns. The thermal lensing effect is such thatplacing one pulse or line too close to a previous one may reduce theefficiency of the index change. By creating a pattern that increases thetime given for heat to dissipate before the laser returns, efficiencycan be increases. For example, if multiple laser scan layers 1, 2, 3, 4,5, 6, 7, and 8 are to be formed in that spatial order (e.g. from deep toshallow, or from shallow to deep), then instead of forming the layers ina time order of layers 1, 2, 3, 4, 5, 6, 7, and 8, the layers may beformed in an interlaced time order such as layers 1, 3, 5, 7, 2, 4, 6,and 8; or 1, 5, 2, 6, 3, 7, 4, and 8; or some other interlaced scheme.Similarly, for the scan lines within a scan layer or the spots within ascan line, the lines or spots may be formed in the interlaced manner.More generally, an interlaced pattern here refers to a laser pulse scanpattern where layers (or lines, or spots) that are immediately adjacenteach other in the spatial order are not immediately adjacent each otherin the time order. Numerical simulations mentioned earlier may be usedto determine what spatial spacing is needed for a given laser pulserepetition rate to avoid unacceptable thermal lensing, so as to designthe interlaced scan pattern accordingly. By generating interlaced scanpatterns, one can generate significant index changes with highefficiency without damaging the lens material.

In another scanning method that utilizes the thermal lensing effect,pre-pulses that have much lower energy than the refractive indexmodifying pulses (e.g., 1:10 to 1:100 of the energy of the refractiveindex modifying pulses) are delivered to the IOL material at suitablelocations to heat the IOL materials to form a transient thermal lens,which will slightly defocus the subsequent refractive index modifyingpulses that immediately follow the pre-pulses. The delay betweenpre-pulse and pulse should be about 100 ps to 100 ns. One practicalbenefit of this technique is to deal with the fact that the patient'scorneal transparency may deviate spot to spot significantly. At placeswhere the corneal transparency is high, the pulse energy that reachesthe IOL material will be stronger; at these places, thermal lensingeffect in the IOL will also be stronger, causing the laser focus spot tobe more defocused, thereby reducing the power density at the focus spot.Thus, the thermal lensing effect can mitigate the undesirable effect ofvariation in the patient's corneal transparency. Another practicalbenefit of thermal lensing is that it allows for the use of opticalsystems with relatively low numerical aperture. In-vivo refractive indexmodification requires relatively low (<0.2) numerical aperture (NA).Small NA is beneficial for cost of the system and efficacy of therefractive index modification. NA less than 0.01 can become dangerous,however, because of the small beam diameter on the retina. Using thepre-pulsing technique, or simply taking advantage of the previoustreatment pulses, to create thermal lens on the way to the retina, thebeam can be defocused, and the light spot on the retina iscorrespondingly larger.

In practice (see FIG. 16), based on the refractive index modificationprofile to be accomplished in a given IOL material, the laser systemparameters may be selected and the scan pattern determined initiallywithout consideration of the thermal lensing effect (step S161). Then,using the initial parameters and scan pattern, the transient refractiveindex change due to thermal lensing effect, as well as its effect on theactual focus spot size of the laser pulses within the IOL and hence theaverage energy density (per unit area) at the focus spot, can bedetermined, for example, by numerical simulation (step S162). The lasersystem parameters and/or the scan pattern may be adjusted (step S164),and the simulation may be re-performed for the adjusted parameters (stepS162), until a satisfactory result is achieved (“Yes” in step S163). Forexample, the adjustment may increase the laser pulse energy if thecalculation indicates that the actual energy density at the focus spot,after taking into consideration of thermal lensing effect, is stillsufficiently below the safety limitation. In another example of stepS164, the laser pulse scan pattern is adjusted to use an interlacedpattern described earlier. The pulsed laser beam is then scanned usingthe adjusted laser system parameters and scan pattern (step S165).

To obtain high refractive index differences within an IOL material,multiple modified layers may be spatially stacked on top of each other,and the refractive index changes of the multiple modified layers add toeach other along the optical path in a generally linear relationship.Similar effects can be generated by use of a laser optical system with arelatively low NA, which forms a longer (in the depth direction) focusspot that can generate the full desired refractive index change of theIOL within one modified layer.

To produce desired refractive index change over a volume of the lens,refractive index change produced by single laser pulses are combined byscanning the pulsed laser beam (“writing”) according to a pattern.Scanning a pattern of laser pulses in the lens loads the lens withthermal energy, as significant amount of energy is absorbed in the IOLas described earlier. The thermal load in the lens need to be carefullymanaged. Numerical simulation, such as thermal FEM modeling, may be usedto calculate expected temperature distribution produced by a pulsedlaser scan pattern. FIG. 17A shows the thermal FEM modeling of an IOLwith uniform laser volume heating of 100 mW for 30 seconds and of a 100um thick layer within the IOL. The represented color graph is thetemperature distribution at the end of the 30 sec heating cycle. FIG.17B shows the time course of selected points within the volume of theeye, including the center of the heating source (max temperature), thecorneal endothelium, and the top surface of the IOL. Such simulationsmay be used to determine the thermal load distribution of given laserscan patterns, and to correspondingly adjust the laser parameters andscan pattern so as to ensure that the thermal load distribution in theeye is within levels safe for human exposure.

For safe human applications, the optical geometry of the laser systemmay be designed to ensure a sufficiently large light distribution areaon the retina in order to reduce light intensity there. Because thelaser beam is focused inside the IOL and then passes through the IOL toreach the retina, and because the IOL has a positive optical power, therefractive power of the IOL will cause the beam spot on the retina to bemore concentrated as compared to when the IOL is not present. To ensurethat safety limits for the retina are satisfied, the beam concentrationeffect of the IOL may be counteract by pre-compensating the input laserbeam. In one embodiment, the pre-compensation is achieved by directingthe laser beam to the IOL at an angled direction that is non-parallel tothe optical axis. As a result, higher laser power may be used to processthe IOL without exceeding the safety limit for the retina, whichimproves the laser processing speed. This is illustrated in FIGS. 18A-B,which show multiple laser beams used sequentially to form multiple laserfocus spots in the IOL. In the case of FIG. 18A, the incident laserbeams are all parallel to the optical axis. Due to the focusing power ofthe IOL, the beams are bent by the IOL toward the optical axis, and as aresult, the multiple laser beams will fall on a smaller retinal areathan had the beams remained parallel to the optical axis after the IOL.In the case of FIG. 18B, the laser beams are incident on the IOL indirections non-parallel to the optical axis (they travel away from theoptical axis); after these laser beams are bent toward the optical axisby the focusing power of the IOL, they become more parallel to theoptical axis than in the case of FIG. 18A and consequently fall on aretinal area that is larger than in the case of FIG. 18A. Larger retinalspot sizes allow higher laser average power and with that fasterprocessing speed. The desired amount of pre-compensation may bedetermined by numerical simulation.

The heat induced refractive index change in IOL materials may bepositive or negative, depending on the laser energy and otherparameters, and may change with time after laser irradiation. After acertain time, such as one day, the change of refractive index willstabilize. Different IOL materials also respond differently to the lasertreatment. For example, the final index change is mostly positive forthe SENSAR® IOL material, but may be negative for some other IOLmaterials, such as for example, acrylic IOL materials having a higherwater content. The amount of induced refractive index change may bemeasured for each IOL material, for example, using a phase shiftinginterferometer.

In practice, for a given IOL material, the amount of induced refractiveindex change, as a function of laser energy and other parameters such asNA, laser pulse duration, laser repetition rate and pattern (such asspot spacing and timing, due to thermal lensing), laser wavelength,etc., is empirically determined. Based on such data, the laserparameters and scan pattern can be designed to achieve a given targetresult of desired refractive index modification of the IOL. Morespecifically, as shown in FIG. 19, for a given IOL material (step S191),its linear absorption coefficient is examined to preliminarily select alaser wavelength range that may potentially be suitable for multi-photoninduced heating (step S192). The sensitivity of the eye for differentwavelength ranges is taken into consideration in this step. For example,FIG. 11, described earlier, illustrates how the suitable wavelengthrange is preliminarily selected for the SENSAR® IOL material. Then, thetwo-photon absorption coefficient of the material as a function of laserpulse energy (or average power density) is measured for selectedwavelengths within the preliminarily selected wavelength range (stepS193). This may be done, for example, by measuring the lighttransmission rate through the sample as a function of pulse energy orpower and then fitting the curves to obtain the threshold andcoefficient parameters. An example of this step for the SENSAR® IOLmaterial is described earlier with reference to FIGS. 12 and 13A-13B.Based on such data, a laser wavelength may be selected to performrefractive index modification for this material (step S194). Then, theamount of permanent refractive index change of the material as afunction of various system parameters is measured (step S195). Forexample, a phase shifting interferometer may be used for suchmeasurement, as described earlier with reference to FIG. 18 as well asFIGS. 6A-9C. With the above data, a laser scan pattern and other lasersystem parameters can be designed to produce a desired refractive indexmodification profile (step S196). The system parameters may include, forexample, laser pulse energy, pulse duration, pulse repetition rate,focus spot size, numerical aperture, etc. The scan pattern parametersmay include, for example, geometric shape formed by the laserirradiation spots, spot spacing, etc. In this step, the selection of thevarious parameters may take into consideration of exposure safety limitsfor the eye. In addition, the designed laser scan pattern and systemparameters may be refined based on other factors and considerations(step S197), such as the self-limiting effect of multi-photon absorptionon the absorption depth described earlier with reference to FIGS.14A-14D and FIG. 15, the self-limiting effect caused by thermal lensingdescribed earlier with reference to FIG. 16, consideration of thermalload distribution described earlier with reference to FIGS. 17A-17B,etc. The refinement may be achieved based on numerical simulations ofthe various effects discussed above.

In an alternative embodiment, by scanning the pulsed laser beam in theIOL in concentric patterns, concentric rings of refractive indexvariation may be generated, forming a Fresnel lens. Such a lens mayprovide high optical power changes (it adds an optical power to theoptical power of the IOL), as high as multiple diopters. In one example,a Fresnel lens formed this way (see FIG. 20) has 6D absolute power asmeasured by phase shifting interferometry as well as wavefrontmeasurements. FIG. 21 shows an example of a Fresnel refractive indexprofile along a radial direction from the lens center. To be a Fresnellens, the phase step, i.e. the size of the jumps between zones in theindex profile, should be an integer number of waves. In this particularexample, the IOL is made of SENSAR® IOL material, and has an edgethickness of 400 μm and a center thickness of 722 μm. A layer of theSENSAR® IOL material 200 μm thick is modified by the laser with avariable index in a number of annular zones (7 in this case) centered onthe optical axis of the IOL. Each zone has a 1 wave difference in phasefrom the inner to the outer edge of the zone, and a 1 wave steptransitioning to the next zone. For example, a 7-zone gradient index,Fresnel diffractive lens with a diameter of about 5 mm, has an opticalpower of 1.333 Diopters. The radial profile in phase has 7 zones of 1wave steps, requiring the gradient refractive index profile shown in thefigure within the 200 μm layer. The example shows a parabolic indexprofile with one wave stepping.

As discussed above, the change in refractive index of the IOL inresponse to laser treatment depends on a multitude of factors, and atthe same time, the laser treatment is limited by various eye safetyconcerns. Therefore, suitable laser system parameters for a refractiveindex modification procedure may vary greatly. In some embodiments, forthe SENSAR® IOL material, the various laser system parameters fallwithin the following preferred ranges. Laser wavelength: 650 to 800 nm,more preferably, 680 to 720 nm; laser pulse energy: 10 nJ to 10 uJ, morepreferably, 100 nJ to 2 uJ; laser pulse duration: 10 fs to 10 ps, morepreferably, 100 to 600 fs; laser pulse repetition rate: 10 to 1000 kHz,more preferably, about 300 kHz; laser focus spot size: 5 to 25 um, morepreferably, 7 to 12 um; numerical aperture (NA) of the incident beam:0.01 to 0.15, more preferably, 0.03 to 0.12; number of repeats(successive laser pulses irradiated at the same position): 1 to 14. Forthe laser scan pattern, the spot spacing in the transverse directionwill typically change with focus spot size and repetition rate; the spotspacing should be sufficiently small to create substantially uniformindex change zone throughout. For a beam with a Gaussian profile, thespot spacing is preferably smaller than the beam spot size. The spotspacing may be different in different scan directions of the scanpattern. In the depth direction, the spot separation is 1 to 100 um, andmore preferably, 3 to 10 um.

In one particular example that used a circular scan pattern, the spotspacing was 2.5 um in the angular direction and 4 um in the radialdirection (i.e. between adjacent circles of the scan pattern), and thebeam had a super-Gaussian profile with an 8 um diameter. In thisexample, the pulse energy was 0.9 uJ, a total of 10.8 J of energy wasdeposited in a 20 mm² area, and the treatment time 0.1 W power was 108seconds. The phase change generated by one layer of modification wasabout 0.06λ, and about 1.2λ, for 20 layers.

In summary, the use of multi-photon absorption allows for the use ofhigh absorption of the IOL material in the UV/blue spectral and in thefar red spectral range, where the photopic sensitivity of the eye isrelatively low. The use of laser wavelengths outside the spectralsensitivity of the human eye allows treatment of patients without thesignificant visual effects during patient exposure and good patientcompliance during the laser treatment. Due to the short pulse durationneeded to get a two photon absorption, effective heating shorter thanthe thermal relaxation time is enabled. Additionally, due to thenon-linear absorption of two or more photons, the exposure in the laserfocal volume is self-limiting as the laser light upfront of the laserfocus will start to be absorbed as soon as the threshold of multiphotonabsorption is reached. Further, the effect of thermal lensing, i.e. thedefocusing of subsequent neighboring laser spots in the scan pattern dueto thermal lensing caused by the previous laser pulses, may be avoidedby placing subsequent laser pulse spots outside of the thermal impactzone of the previous pulses; the thermal lensing effect may also betaken advantage of to defocus the laser spots which allows for higherpulse energy to be used. Also, the overall thermal management of theinduced thermal load within the IOL and surrounding tissue becomes andimportant practical consideration, as overloading the IOL andsurrounding tissue with heat should be avoided to avoid thermal damage.

The refractive index modification methods described above may also beused for customization of IOLs during production, or in-officemodification after production but before implantation into patients'eyes. In such applications, the wavelength restrictions and the eyesafety considerations are eliminated because no patient's sys ispresent, and higher laser power may be used to increase the processingspeed. In an in-office modification process, the target refractive indexmodification is customized for the intended patient, and the laser scanpatterns is designed to achieve such a target modification.

In addition to IOLs, the refractive index modification methods describedabove may also be used to modify the refractive properties of contactlenses. FIGS. 22A (phase contrast) and 22B (bright field) shows aFresnel lens pattern written in a contact lens, in this example, anEtafilcon A contact lens with 58% water, 1 day Acuvue Moist, with 50-125nJ pulse energy and 12 pattern repeats. This method can be used tocustomize contact lenses.

In various embodiments described above, the methods for modifyingrefractive index of the IOL material may be carried out by the lasersystem describe earlier which includes the control electronics 210. Thecontrol electronics 210 may include a computer, microcontroller, etc.,and associated memory devices that store computer readable program code.The computer or microcontroller executes the computer readable programcode to control the laser light source 200 and other components of thelaser system 200 to execute the above described methods.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. The term “connected” is to beconstrued as partly or wholly contained within, attached to, or joinedtogether, even if there is something intervening. Recitation of rangesof values herein are merely intended to serve as a shorthand method ofreferring individually to each separate value falling within the range,unless otherwise indicated herein, and each separate value isincorporated into the specification as if it were individually recitedherein. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein, is intended merely to betterilluminate embodiments of the invention and does not pose a limitationon the scope of the invention unless otherwise claimed. No language inthe specification should be construed as indicating any non-claimedelement as essential to the practice of the invention.

While certain illustrated embodiments of this disclosure have been shownand described in an exemplary form with a certain degree ofparticularity, those skilled in the art will understand that theembodiments are provided by way of example only, and that variousvariations can be made without departing from the spirit or scope of theinvention. Thus, it is intended that this disclosure cover allmodifications, alternative constructions, changes, substitutions,variations, as well as the combinations and arrangements of parts,structures, and steps that come within the spirit and scope of theinvention as generally expressed by the following claims and theirequivalents.

The invention claimed is:
 1. A method of altering a refractive propertyof an implantable intraocular lens having an optic body including anoptical zone and a peripheral zone surrounding the optical zone,comprising: implanting the intraocular lens in a patient's eye;generating a pulsed laser beam using a pulsed laser source and a lightdelivery optical system, the pulsed laser beam having a wavelength of650 to 800 nm, a pulse energy of 10 nJ to 10 uJ, a pulse duration of 10fs to 10 ps, a pulse repetition rate of 10 to 1000 kHz, a laser focusspot size of 5 to 25 um, and a numerical aperture of 0.01 to 0.15; whilethe intraocular lens is in the patient's eye, irradiating the opticalzone of the intraocular lens with the pulsed laser beam, wherein theoptical zone comprises a crosslinked acrylic polymer material configuredto change its refractive index upon irradiation by the pulsed laserbeam, thereby altering a refractive property of the intraocular lens. 2.The method of claim 1, wherein a first change in the refractive index isnegative during a first time period after irradiation and a secondchange in the refractive index is positive in a second time period afterirradiation.
 3. The method of claim 1, wherein the change in refractiveindex relative to the pre-irradiation refractive index at a locationwithin the crosslinked acrylic polymer is linearly related with a totalenergy of the irradiation with the light source within a defined totalenergy range.
 4. The method of claim 1, wherein the pulsed laser beamhas a wavelength of 680 to 720 nm, a pulse energy of 100 nJ to 2 uJ, apulse duration of 100 to 600 fs, a pulse repetition rate of 300 kHz, alaser focus spot size of 7 to 12 um, and a numerical aperture of 0.03 to0.12.
 5. A method of altering a refractive property of an implantableintraocular lens having an optic body including an optical zone and aperipheral zone surrounding the optical zone, comprising: generating apulsed laser beam using a pulsed laser source and a light deliveryoptical system; calculating a scan pattern based on a pre-definedrefractive index modification profile for the optical zone of theintraocular lens and a multi-photon absorption-induced shift inabsorption depth in the optical zone corresponding to a pulse energy ofthe pulsed laser beam; and irradiating the optical zone of theintraocular lens with the pulsed laser beam, including scanning a focusspot of the pulsed laser beam within the optical zone according to thescan pattern, wherein the optical zone comprises a material configuredto change its refractive index upon irradiation by the pulsed laserbeam, thereby altering a refractive property of the intraocular lens. 6.The method of claim 5, wherein the calculating step includes: definingan initial scan pattern based on a profile of changes of the refractiveindex to be produced in the optical zone; selecting a laser pulse energyof the pulsed laser source and a focal distance and a numerical apertureof the light delivery optical system; based on the selected laser pulseenergy, focal distance and numerical aperture, and material propertiesof the optical zone, calculating a shift value in absorption depthcaused by multiphoton absorption by the optical zone; and calculatingthe scan pattern by moving the initial scan pattern to a deeper locationbased on the calculated shift value.
 7. A method of altering arefractive property of an implantable intraocular lens having an opticbody including an optical zone and a peripheral zone surrounding theoptical zone, comprising: generating a pulsed laser beam using a pulsedlaser source and a light delivery optical system; calculating a scanpattern based on a pre-defined refractive index modification profile forthe optical zone of the intraocular lens and a thermal lensing effect onsubsequent laser pulses caused by a temperature gradient in the opticalzone induced by previous laser pulses of the pulsed laser beam; andirradiating the optical zone of the intraocular lens with the pulsedlaser beam, including scanning a focus spot of the pulsed laser beamwithin the optical zone according to the scan pattern, wherein theoptical zone comprises a material configured to change its refractiveindex upon irradiation by the pulsed laser beam, thereby altering arefractive property of the intraocular lens.
 8. A method of altering arefractive property of an implantable intraocular lens having an opticbody including an optical zone and a peripheral zone surrounding theoptical zone, comprising: generating a pulsed laser beam using a pulsedlaser source and a light delivery optical system; defining a scanpattern based on a profile of changes of the refractive index to beproduced in the optical zone of the intraocular lens, the scan patternincluding a plurality of scan layers arranged in a spatial orderaccording to their depths; and irradiating the optical zone of theintraocular lens with the pulsed laser beam, including scanning a focusspot of the pulsed laser beam within the optical zone to form theplurality of scan layers one at a time according to a time order,wherein an order of the plurality of scan layers in the time order isdifferent from an order of the plurality of scan layers in the spatialorder, wherein any scan layers that are immediately adjacent each otherin the spatial order are not immediately adjacent each other in the timeorder, wherein the optical zone comprises a material configured tochange its refractive index upon irradiation by the pulsed laser beam,thereby altering a refractive property of the intraocular lens.
 9. Themethod of claim 5, wherein the scan pattern is configured to produce arefractive index modification profile in the optical zone having aplurality of concentric rings that form a Fresnel lens.
 10. The methodof claim 5, wherein the light beam has a wavelength of 400 to 450 nm or650 to 800 nm.
 11. The method of claim 5, wherein the pulsed laser beamhas a wavelength of 650 to 800 nm, a pulse energy of 10 nJ to 10 uJ, apulse duration of 10 fs to 10 ps, a pulse repetition rate of 10 to 1000kHz, a laser focus spot size of 5 to 25 um, and a numerical aperture of0.01 to 0.15.
 12. The method of claim 7, wherein the scan pattern isconfigured to produce a refractive index modification profile in theoptical zone having a plurality of concentric rings that form a Fresnellens.
 13. The method of claim 7, wherein the light beam has a wavelengthof 400 to 450 nm or 650 to 800 nm.
 14. The method of claim 7, whereinthe pulsed laser beam has a wavelength of 650 to 800 nm, a pulse energyof 10 nJ to 10 uJ, a pulse duration of 10 fs to 10 ps, a pulserepetition rate of 10 to 1000 kHz, a laser focus spot size of 5 to 25um, and a numerical aperture of 0.01 to 0.15.
 15. The method of claim 8,wherein the scan pattern is configured to produce a refractive indexmodification profile in the optical zone having a plurality ofconcentric rings that form a Fresnel lens.
 16. The method of claim 8,wherein the light beam has a wavelength of 400 to 450 nm or 650 to 800nm.
 17. The method of claim 8, wherein the pulsed laser beam has awavelength of 650 to 800 nm, a pulse energy of 10 nJ to 10 uJ, a pulseduration of 10 fs to 10 ps, a pulse repetition rate of 10 to 1000 kHz, alaser focus spot size of 5 to 25 um, and a numerical aperture of 0.01 to0.15.